Genome-Wide Scan for Loci of Adolescent Obesity and Their Relationship with Blood Pressure
Hypertension, a disorder that is generally emerged during adulthood, is now becoming more and more popular in the adolescents. The cause of this phenomenon is presumed to be the increasing occurance of adolescent obesity. Overview Since obesity and hypertension are frequently cosegregated in family, there could be a shared genetic architecture between the traits. Melka and her colleagues attempted to find the relationship and connection between obesity and hypertension. They conducted a genotype-phenotype association study to find out if genome-wide identified obesity gene loci are associated with blood pressure elevation, in which they conducted a GWAS to search for SNPs associated with obesity, and tried to link them to hypertension. Background: Body Mass Index (BMI) Body mass index, also known as Quetelet index, is a numeric measurement a person's "thickness" (body shape) based on mass and height. Established by Belgian polymath Adolphe Quetelet in the mid 1800s, BMI is calculated by equation : BMI = (Body mass (kg))/(Height (m))^2. Background: Genetic Founder Effect Genetic founder effect is decrease in genetic diversity when a new population is establish by a small number of individuals from a much larger group. This new population will have reduced genetic variation comparing to the original and non-random sample of genes in the original group. Some genetic traits will vanish, while some may become abundant. Procedure A total of 598 Caucasian adolescents, aged 12 to 18 year-old, were recruited from a French-Canadian population with known genetic founder effect. All the recruits went through a 15-hour cardiovascular (including average of systolic and diastolic blood pressure during five sections of a 52-minute cardiovascular protocol), metabolic (total fat mass, TFM) and behavioral phenotyping. They were also genotyped with Illumina Human610-Quad Beadchip (582,539 SNP). Finally, the authors identified loci that had P values less than 5*10^-4 from those indetified loci used in the current GWAS of BMI and TFM, and examined them for association with blood pressure using mix-model analysis. Results GWAS of BMI and TFM showed two novel obesity loci:paired box 5 (PAX5)locus and mitochondrial ribosomal protein S22 gene (MRPS22) locus; and three previously identified and validated obesity loci that had P value less than 5*10^-4 (this specific value was used because they decided to study the three loci that had the smallest P value among the eight candidate genes, and the best P value they could get started from 5*10^-4), they are melanocortin-4 reporter (MC4R), fat mass- and obesity-associated (FTO), and mitachondrial carrier homolog 2 (MTCH2). These 5 loci were examined for assosiation with blood pressure, and the results demonstrated that PAX5, MRPS22 and FTO were associated with blood pressure, while MC4R and MTCH2 were not associated with blood pressure. Discussion The mechanisms that underline adiposity regulation by the two novel obesity loci, PAX5 and MRPS22, are not clear at the time. It is assumed that they are involved in lipolysis and energy burning, but further investigation is still required on this subject. The significance of this study is that it shows, out of the five (PAX5, MRPS22, MC4R, FTO, and MTCH2) obesity loci studied in this research, only three (PAX5, MRPS22, and FTO) of them are associated with blood pressure. This suggests that only certain genetically defined types of obesity could induce the development of hypertension. Furthermore, these findings are very hopeful. These three loci (PAX5, MRPS22, and FTO) could potentially be targets for obesity and hypertension gene therapy. With appropriate gene therapy that targets these three loci, it is possible to treat or decrease the occurance of obesity and hypertension at the same time. Reference 1. Melka, M., et al. The Journal of Clinical Endocrinology & Metabolism (2012) 97 (1): E145, Genome-Wide Scan for Loci of Adolescent Obesity and Their Relationship with Blood Pressure http://jcem.endojournals.org/content/97/1/E145.long 2.Body Mass Index http://www.cdc.gov/healthyweight/assessing/bmi/ 3. Genetic Founder Effect: http://evolution.berkeley.edu/evosite/evo101/IIID3Bottlenecks.shtml 4. Genetic Founder Effect: http://www.wisegeek.com/what-is-the-founder-effect.htm